The applicant proposes to continue and extend studies of adipose tissue morphology and function, in leanness and obesity, in different locations of the adipose organ and in several mammalian species, including the human. The objectives of the research are directed toward elucidation of the following topics: 1) The mode of enlargement of the adipose organ in relation to age and nutrition; 2) The relation between fat cell volume, the metabolic activities and the hormonal responsiveness of the adipose cells, in subjects with varying degrees of adiposity; 3) Mechanisms responsible for the loss of responsiveness of enlarged fat cells to the glucose-transport stimulating effect of insulin; 4) Evaluation of the overall contribution of the adipose organ to the carbohydrate and lipid metabolism of the organism. Characterization of adipose tissue in terms of fat cell size and number has recently been developed in several laboratories, including the applicant's. The integration of the morphological observations with the determination of the fat cell's biochemical functions (glucose uptake, fatty acid synthesis, lipid storage, fat mobilization) will allow determination of the tissue's metabolic activities and their hormonal regulation on the basis of fat cell number and in relation to the adipocyte size. Several aspects of adipose tissue physiology and pathology will be studied.